Triple Negative Breast Cancer Integrative Options 

TripleNegativeFightFirst a definition of Triple Negative Breast Cancer. The informative video below defines what it is, what the problems are and introduces the concept of “cancer stem cells” which is central to both mainstream personalized targets as well as integrative options. Mainstream personalized options may be less robust than those who are positive for Her-2 or hormone receptors, but if you have been misled that there are none, this is simply not true. The prognosis for this group, as you know because you are reading this and looking for solutions, is considered to be worse than for most breast cancers. Recurrences are very likely and occur within three years, usually in visceral organs like the liver.

However, even though this is true for the first five years, if you are a survivor past that point the prognosis improves dramatically and is roughly similar to that of other types of breast cancer. The mission is therefore to do everything possible in addition to chemotherapy, after local tumor therapy, to get to the five year mark and beyond. Most patients do no know better and are not advised to consider their options beyond chemo.  As far as mainstream local and chemotherapy, the NCCN Guidelines for breast cancer apply, so please review those based on your stage.

  

Rethinking HER-2 Negative Treatment Options

Advances in breast cancer are developing faster than in most other cancers. This is because of the massive focused research effort, from basic laboratory science research to clinical trials. In hormone and HER-2 positive patients, it has become possible to dramatically extend quality of life filled years and increase chances of cure because of “personalized” and “targeted” therapies. You can learn more about these from the main breast cancer information page on this site, but you have probably been told that these will not work for you and that chemo is the only option, other than hope.  Based on clinical trials data, for example from NSABP-B31, this may be true.  For breast cancer to be categorized HER-2 positive (and the patient to be eligible for HER-2 targeting drugs like trastuzumab), the tumor cells must either stain strongly (3+) using immunohistochemistry (IHC) or the HER-2 gene must be amplified (an abnormally high number of copies of that gene) has to be detected by using fluorescence in-situ hybridization (FISH).  However, re-analysis of some of this data regarding HER-2 negative patients, has yielded surprising results. Basically, it was uncovered that patients who had much lower expression of HER-2 (now called “low”, but were originally called “negative” for the study from the criteria listed above) benefited just as much as HER-2 over-expressed or positive patients.  The good news is that most patients who are “negative” are actually just “low” in expression of HER-2 and therefore may benefit from Trastuzumab or similar HER-2 receptor targeting bio-drugs.

Rethinking Hormone Receptor Negative Treatment Options

Regarding hormone receptor negative results, which is the other two pieces of the triple negative picture, there are similar questions. A “negative” test by IHC test does not always mean zero receptors, but it does mean a very low number occupying <1% of the tumor. Therefore, using anti-estrogenic or progesterone modulating therapy is still something to consider, depending up the actual test result level. The College of American Pathologists(CAP) and the American Society for Clinical Oncologists (ASCO) have a set of quality guidelines (for all three receptor markers, ER, PR and HER-2), but there may be some variations between laboratories. So, if a specimen is read negative for either estrogen (ER) or progesterone receptor(PR), especially at a low volume laboratory, it is reasonable to ask if the results could be run at another higher volume lab. In addition, there are similar retrospective studies where re-review of the original study results show that even patients who are negative for ER or PR may benefit from Megace,a progesterone hormone, which blocks receptors among other unclear anti-cancer actions. A small prospective study confirms this, at least in multiply recurrent patients.

Developing Molecular Targets and Clinical Trials

Because of the surprising results on retrospective re-review of the HER2 data there is a clinical trial, NSABP/NRG B47, that is enrolling patients to determine if these surprising results can be verified and if many of the currently classified HER-2 negative patients will benefit from this type of targeted therapy. Study completion is slated for 2017, so it is still enrolling as of early 2015.

Research in this area is very robust and clinical trials are underway to test other targeted molecular pathways.  For example,  Epidermal growth factor receptor (EGFR) is overexpressed in half of triplenegative breast cancers, which makes it a seemingly great target.  However,  EGFR inhibitors (e..g. currently lapatinib, everolimus and others) have clinically not worked well in metastatic breast cancer.  While this seemed like a dead end at first, it was found that inhibiting another target called mTOR  with agents like rapamycin can reverse the apparent ineffectiveness of EGFR inhibitors.  This is undergoing clinical trials, and is only the very tiny tip of the rapidly growing iceberg of potential targets and pathways that can be inhibited.  For the moment, there is no obvious targeted molecular pathway, but it should not be long before many are uncovered.  Meanwhile, what can be done other than wait?  Participation in triple negative breast cancer clinical trials is one option.

Luteinizing Hormone Releasing Hormone (LHRH) agonists, like leuprolide and goserelin exist and have been used in prostate cancer treatment for a long time. Now there is developing data that it might have a benefit in triple negative breast cancer. This is something to discuss with your oncologist, absent other options.

If you need a little review about receptors and how these become molecular targets, click HERE.

Triple Negative Breast Cancer Natural and Nutritional Support Options

To some degree integrative approaches can also be of benefit because in some cases the same metabolic pathways are targeted with natural substances and dietary strategies, but also for another reason involving epigenetics, nutrigenomics and the concept of “cancer stem cells“. The video above introduced the idea that perhaps there are more cancer stem cells in more aggressive cancer variants, like triple negative breast cancer. Now watch the video below to get a quick definition and  better visual idea about how cancer stem cells behave.

Review of the best scientifically based natural or “off label” mainstream options is always under revision or being updated, or additional articles are linked in. However, the overarching basic concept is what while we are awaiting mainstream targeted molecular therapies against cancer stem cells we can use natural substances and nutrition to influence epigenetic change and control over these slow growing cancer stem cells as well as general immune strengthening which should improve anti-cancer immuno-surveillance and immuno-editing. Much of this can be applied to breast cancer in general, or even to other cancers. However, quite a bit of what follows has been looked at specifically in Triple Negative Breast Cancer. This following short video should also pique interest.

Nutritional Dietary Base and Key Supplements
It is critical to lay down the basic anti-cancer diet first, rather than maintaining a hit & miss diet plus gobs of supplements to try to fix the broken diet. Mother Nature designed food to work much better together than apart. This is because of synergies between micro and macro nutrients contained in food, some of which we know about and others that are yet a mystery. Nutrients work together like a finely tuned orchestra, which is better than putting together a dilapidated garage band of poorly matched musical instruments. That would be similar to randomly picking and choosing, mixing and matching synthetic and “natural” vitamins and supplements. Neither you nor I are smarter than Mother Nature.

Ketogenic diet +/- Metformin : cannot be long term solution due to bone and kidney health and side effects. There is a lot of research currently going on in this area regarding cancer. This diet has been used effectively for years in epilepsy seizure control, and then showed promise in certain brain tumors. Currently it is in clinical trials for multiple types of cancer, including breast cancer survivorship. One study was called the KOLIBRI study and was completed in 2016.  The data is not yet published. The idea at the very basic level is to minimize sugar intake and insulin spikes which “feeds the cancer”. One cannot eliminate all simple carbohydrates and your body will make glucose from protein in the liver anyway. However you can definitely minimize it. Metformin, used in diabetes, further reduces the circulating sugar but its anti-cancer activity may extend beyond this biological function. The drawback, and the reason it is usually only a short term intervention, is that it is hard to tolerate and can damage bone and other organs. It is also an “acidic diet”, which goes against the concept of trying to keep a minimal daily acid load. Having said that, while it is true that the standard American diet (SAD) generates a daily net positive acid load (in mili-moles or very tiny amounts), there is not a shred of evidence that an “alkaline diet” is anti-cancer per se.

The greatest amount of anti-cancer evidence is for an “old school” Mediterranean Diet or, a little more extreme, a WholeFood Plant Based Diet with particular attention to the following ingredients. Both of these diets are anti-inflammatory anti-oxidant in nature and form the base for a long term diet. They can also be quite “alkaline”, if you choose to follow the “alkaline” path despite lack of evidence, depending upon the veggies your select. Some are more alkaline than others and you can avoid buying expensive and useless alkaline miracle water. The “additional” ingredients are either part of these diets already or they should be kept in mind for inclusion.

  • blueberries & berries in general for fruits, not melons
  • curcumin/piperine
  • carnosol polyphenol
  • EGCA
  • pectin
  • Shitake and Maitake mushrooms
  • sulphorafanes
  • Fish or Omega supplementation if vegan/vegetarian

Supplementation is a short list. This is because all of the current best anti-cancer data points to whole food solutions, with a few exceptions as noted below:

  • vitamin D 2000-3000IU/day, but measure blood levels first
  • calcium 2000mg total, including any dietary intake, which is especially important if not consuming dairy
  • B12 methyl-cobalamin and B complex if vegan/vegetarian
  • “Breast Defend”: medicinal mushrooms (Coriolus versicolor, Ganoderma lucidum, Phellinus linteus), medicinal herbs (Scutellaria barbata, Astragalus membranaceus, Curcuma longa), and purified biologically active nutritional compounds (diindolylmethane and quercetin). This product has some specific basic evidence for its use and the ingredients within are certainly plausible cancer fighting components.
  • Stevia root is not a supplement per se, but if you have a sweet tooth this is an excellent natural sweetener.

 

Other additions would include the following strategies:

  • XenoEstrogen “detox”: Based on the issues about hormone receptors above, this applies more to ER+ cancers, but it still worth considering because of the nature of endocrine disruptor xeno-estrogens, which are essentially toxins to your body. Periodic “detox programs” are useless, because the body is exposed to 65,000 or more chemicals per year and being assaulted every day. Detox has to be ongoing every day, and this is a different topic covered elsewhere. Suffice it to say that plastics, hormones used in raising animals, and all sorts of chemicals are out there that you must uncover and avoid.
  • Leptin serum levels can be elevated in breast cancer and are associated with poor prognosis. Leptin is your “stop appetite” hormone, while Ghrelin is your hunger hormone. But when you become resistant to leptin, you end up wanting to eat more. Furthermore, low levels of adiponectin along with elevated leptin may be the worst case scenario. Imbalance here also leads to obesity, which may be part of the cancer promoting story in this area. Mainstream biological agents to modulate this are being investigated but are early in development. Meanwhile, diet and exercise reverses leptin resistance and balances this hormonal picture. This is just ONE of the pathways which shows that it is time to get ultra-serious about exercise in cancer recovery and survivorship. Until I add more on this topic, review THIS STORY HERE, in addition to getting your anti-cancer diet and exercise programs into gear.

For more on the overlap between the concepts of epigenetics, nutrigenomics and cancer stem cells please take a look at the integrative breast cancer treatment options story HERE. The story is evolving but it is quite clear that nutrition, on the positive side, and negative environmental influences, on the negative side, can significantly affect cancer stem cells. This is what makes it critical to make better lifestyle choices and repair those that may have contributed to the root cause of your cancer. While no one has proven this beyond the shadow of a doubt, it makes a lot of sense, it is scientifically plausible, it is low risk and there is really nothing to lose and your life to gain.

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